UNCLASSIFIED

Universal Test & Treat

trials: What they tell us

about HIV Epidemic

Control in 2019

UNCLASSIFIED

What do the Universal HIV test and treat (UTT) trials tell us about HIV

Epidemic Control in 2019?

UNCLASSIFIED

“First Generation” Universal Test and Treat Trials

› Randomized, population-based combination intervention studiesintegrating HIV testing, prevention and treatment

› Conducted in Southern and Eastern Africa across a range of HIV prevalence

› Conducted during global transitions to “treat all”, “differentiated care,” and rapid ART start

› Pre-dated PrEP roll-out

› Short follow-up ~3 years

› Used measurement approaches that impacted outcomes (HIV diagnosis, viral suppression, and possibly behavior) in intervention and control arms

UNCLASSIFIED

Trial BCPP/Ya Tsie PopART SEARCH TasP

Country Botswana South Africa / Zambia Kenya / Uganda South Africa

Prevalence 29% 22% 4-19% 30%

Arm C I CI

Arm A

I

Arm BC I C I

Universal testing -

Home,

mobile

-

Home +

field

(men,

youth)

Home +

field

(men,

youth)

Multi-dz

Fairs/

Home

Multi-dz

Fairs/

Home

Home

Home

Testing frequencyBaseline;

ongoing

targeted

Ongoing

Annual

Ongoing

~AnnualBaseline Annual 6 monthly 6 monthly

Enhanced linkage

Rapid ART Start

(from 2016)

Universal Treatment

(from 2016)

(from 2016)

(from

2016)

(from 2016)

(from

2016)

Differentiated ART

Delivery

(Zambia)

(Zambia)

UTT TrialDesigns

UNCLASSIFIED

Study Interventions: Universal HIV testing

Goal: Ensure all PLHIV are HIV tested (or retested) and offered rapid ART start

1. Persons not previously HIV diagnosed (and newly-infected, as soon as possible)

2. Persons already diagnosed with HIV but who have not started ART

or who have fallen out of care

Approach: “Out of facility” (increase access, reduce stigma)

Community partnerships and mobilization followed by

1. Home testing & mobile testing (BCPP, PopART, TasP)

2. Multi-disease health fairs followed by home testing for non-participants (SEARCH)

3. Demand generation strategies for men and youth

4. Repeated regularly (6 monthly or yearly)

UNCLASSIFIED

Study Interventions: Linkage & ART start

› Goal: Ensure all PLHIV out of care are offered rapid linkage

and ART start upon HIV testing

› Approach: Patient-centered interventions to bridge out-of-

facility testing to clinic with ongoing retention support

1. Health workers facilitated linkage from home or health fair testing

2. Rapid ART start (same-day with starter packs or 1st clinic visit)

3. Supportive (not punitive) clinic environment, text appointment reminders

with tracking, men & youth ”friendly, multi-disease (SEARCH)

UNCLASSIFIED

1st 90: Known HIV Status / All HIV+

With UTT, >90%

of all PLHIV were

tested (1st 90)

› Achieved within 1-2 of

years in some studies

› In a variety settings-

urban and remote rural

84%

57%62%

79%

93% 91% 92% 92%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

BCPP PopART SEARCH TasP

Baseline End of Study*Intervention arms only.

PopART Intervention arms combined

UNCLASSIFIED

2nd 90: On ART/HIV DiagnosedWith UTT, 3

studies started

ART in ~90-97%

(2nd 90)

› Rapid linkage and

much faster ART start

in intervention arms

› Low linkage in TasP,

but ART initiation high

once linked to clinics

85%

78%81%

37%

97%

88%

95%

58%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

BCPP PopART SEARCH TasP

Baseline End of Study*Intervention arms only.

PopART Intervention arms combined

UNCLASSIFIED

3rd 90: Virally suppressed/on ARTWith UTT, all

studies reached

viral suppression

~90% if on ART

(3rd 90)

97%

89%84%

79%

97%

87%90%

87%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

BCPP PopART SEARCH TasP

Baseline End of Study*Intervention arms only.

PopART Intervention arms combined

UNCLASSIFIED

Population-Level Viral SuppressionWith UTT,

3 studies reached

Population-level

viral suppression

>73%

› Dramatic increases in

population viral

suppression over short

period of time

› From low (23%) or high

(70%) starting point

70%

57%

42%

23%

88%

74%79%

46%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

BCPP PopART SEARCH TasP

Baseline End of Study*Intervention arms only.

PopART Intervention arms combined

UNCLASSIFIED

Population-Level Viral Suppression by SexInterventions

effectively

increased

population level

suppression in

both men and

women

*Intervention arms only.

PopART Intervention arms combinedBaseline End of Study

86%90%

71%74% 74%

81%

43%47%

66%

72%

41%

59%

37%

45%

19%

25%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Men Women Men Women Men Women Men Women

BCPP PopART SEARCH TasP

UNCLASSIFIED

Population-Level Viral Suppression: YouthInterventions

showed variable gains in youth

› Suppression among youth still remains low in all studies

› Contributions from new infections and worse ART uptake and outcomes

*Intervention arms only.

PopART Intervention arms combinedBaseline End of Study

76%

90%

61%

76%

55%

80%

25%

50%

43%

72%

38%

57%

25%

44%

6%

27%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

16-24 >=25 18-24 >=25 15-24 >=25 16-24 >=25

BCPP PopART SEARCH TasP

UNCLASSIFIED

UTT Population-Level Viral

Suppression Exceeds Current

“Standard of Care” in most

African Countries

Country VS Ref: El-Sadr, NEJM, 2019,

and UNAIDS Report

Population-Level Viral Suppression

55% 55%

42%

58%

46%

88%

74%79%

46%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Country Data UTT Trial Data

UNCLASSIFIED

Summary: Universal testing and treatment is feasible

1. UTT rapidly increased population-level viral suppression levels exceeding most SSA country level estimates› Across a spectrum of HIV prevalence, baseline viral suppression› Using different approaches, but with key commonalities

2. Universal testing both re-engaged prior HIV+s to care and identified new HIV infections› Robust linkage and rapid ART start interventions increased viral

suppression

3. Achieved substantial increases in suppression among men and youth› Disparities in some cases reduced, but not eliminated

UNCLASSIFIED

Did implementation of UTT reduce HIV incidence?

UNCLASSIFIED

1. HIV incidence effect (~20-30% reduction) observed when UTT compared to a control without universal testing (BCPP & PopART)

2. HIV incidence reduced (~30%) in both arms when control arm had universal testing (SEARCH)› 32% reduction observed between years 1 and 3

(SEARCH intervention arm)

Note: Impact of UTT intervention in trials setting (vs national-scale up) was almost certainly underestimated, due to mixing outside of intervention communities

HIV Incidence findings

› Population-level

outcome

› Reflect very short time

frame of these trials (~3

years)

UNCLASSIFIED

HIV incidence outcomes

Trial BCPP PopART SEARCH TasP

Country BotswanaSouth Africa /

ZambiaKenya / Uganda South Africa

Arm C I C I C I C I

Universal testing - -

Universal treatment - -/ -/ -/ -

Population viral

suppression

- at start 75% 70% 52% 57% 42% 42% 26% 24%

- at end 83% 88% 68% 74% 68% 79% 45% 46%

- difference +8 +18 +16 +17 +26 +37 +19 +23

HIV incidence

Annual incidence for

100 person-years0.92 0.59 1.55 1.24 0.27 0.25 2.27 2.11

Reduction (I vs C) 31% reduction 20% reduction

not significant,but 32% reduction in

intervention arm

between years 1 & 3

not significantNote:

both intervention arms

were pooled for PopART.

UNCLASSIFIED

Population viremia correlated with incidence

› Fewer people with viremia associated with fewer transmissions

› Seen across all studies

› Heterogeneity as expected

› mobility, external infections, network structure

UTT consortium, confidential, unpublished, not for distribution

0.00

0.50

1.00

1.50

2.00

2.50

3.00

3.50

72% 74% 76% 78% 80% 82% 84% 86% 88% 90% 92% 94% 96% 98% 100%

HIV

Inci

den

ce (

per

10

0P

Y)

Proportion of population HIV-negative or virally suppressed

SEARCH Control SEARCH Intervention TASP Control

TASP Intervention BCPP Control BCPP Intervention

PopART Control PopART Intervention

UNCLASSIFIED

Should we do UTT? the investment case

YESSolid evidence that UTT can rapidly achieve high levels of viral suppression and reduce HIV incidence faster than standard of care

› UTT may also be the most effective way to rapidly reduce mortality

› Universal Testing is a gateway for prevention (e.g. PrEP)

› UTT costs could be shared using multi-disease approach and improve outcomes of other diseases

NOUTT cannot and will never lead to HIV elimination

› Universal Testing is too costly

› Need for universal testing in current landscape (PrEP) has not been directly quantified

› Targeted testing of high-risk persons is sufficient (including partner notification)